Wetness of the ocular surface and other exposed mucosae is maintained by a continuous aqueous fluid secretion produced by exocrine glands. Disturbances of this process lead to eye, mouth and vaginal dryness syndromes that are highly prevalent, particularly among aged persons (Moss, S. E., et al. 2008. Optom. Vis. Sci. 85:668-674; Barker, K. E. & Savage, N. W. 2005. Aust. Dent. J. 50:220-223; Leiblum, S. R., et al. 2009. J. Sex Med 6:2425-2433). In the eye, basal tear flow is adjusted to variations in environmental conditions and blinking rate. Tear flow occurring in the absence of emotional or exogenous irritant stimuli (‘basal’ tear secretion) is adjusted to variations in environmental conditions and blinking rate (Dartt, D. A. 2009, Prog. Retin. Eye Res. 28:155-177). Tearing also increases markedly upon ocular surface irritation (Acosta, M. C. et al. 2004. Invest Ophthalmol. Vis. Sci. 45:2333-2336). Irritating stimuli are detected by mechano-nociceptor and polymodal nociceptor trigeminal nerve endings sensitive to injurious mechanical forces, noxious heat and irritant chemicals, that evoke pain (Belmonte, C., et al. 2004. Exp. Eye Res. 78:513-525) and irritation-induced tearing. However, the neural structures responsible of sensing ocular surface dryness to regulate basal tearing rate remain undefined.
Xerophthalmia or dry eye syndrome is a disease characterised by persistent dryness of the conjunctiva and opacity of the cornea.
Multiple causes can lead to xerophthalmia, which is more common in elderly people. Amongst diseases causing xerophthalmia are found: vitamin A deficit, Sjögren syndrome, rheumatoid arthritis and other rheumatologic diseases, chemical or thermal burns, drugs such as atenolol, chlorpheniramine, hydrochlorothiazide, isotretinoin, ketorolac, ketotifen, levocabastin, levofloxacin, oxybutynin, tolterodine.
Treatments used to treat xerophthalmia include corticosteroids which may be effective in early stages of the disease, vitamine A supplements and pilocarpine which is a drug that increases tear production. Among improve dryness preparations (artificial tears), solutions of hypromellose and carbomer gels which are applied to the conjunctiva are used. However, these treatments have a clear limitation regarding its efficacy and toxicity. Therefore, there is a need to provide new improved treatments for, xerophthalmia, vaginal dryness and dry mouth syndrome.